1. Field of the Invention
The present invention relates to pharmaceutical compositions. More specifically, it relates to the use of pharmaceutically acceptable vehicles comprised of (i) a modified liquid carrier and (ii) an unmodified carrier, wherein the ratio by volume of the modified liquid carrier to the essentially un-oxidizable carrier is between 0.00001:99.99999 to less than 0.01:99.99, that provide the composition with predictable sustained-release properties.
2. Background of the Invention
In the pharmaceutical arts, drug delivery is an element as significant as drug activity. Many drugs or bioactive agents with apparent in vitro activity fail at the clinical level due to the inability to prepare, store, or deliver the bioactive agent to the site of action in effective concentrations over a sufficient period of time.
A vehicle for the stable storage and effective delivery profile of a bioactive agent is of great utility. Those skilled in the art will understand that storage stability and effective delivery profile are, to some extent, specific to bioactive agents, the condition for which the bioactive agent is administered, and the presenting condition of the subject.
Sustained-release or oil-based preparations are considered in WO 97/49402 (Vlaminck); WO 94/00105 (Sabater); U.S. Pat. No. 4,297,353 (Hawkins); U.S. Pat. No. 5,019,395 (Mahjour); U.S. Pat. No. 5,739,159 (Wolf); U.S. Pat. No. 5,162,057 (Akiyama); WO 96/20698 (Levy); the teachings of which are incorporated herein by reference. Also incorporated by reference is WO 98/41207 (Brown) addressing subcutaneous administration of antibiotic into the ear of an animal.
U.S. Pat. No. 5,721,359 discloses the molecule crystalline ceftiofur free acid (CCFA), which is a cephalosporin antibiotic intended for use in mammals, and in particular food animals (e.g., cattle, sheep, goats and swine). The patent suggests that oil suspensions of CCFA can be produced for administration to food animals where the oils are vegetable oils. The oils as disclosed in the patent are intended to be used in their natural form. An advantage of this molecule over other antibiotics, particularly those in the ceftiofur family, is that it can be used to prepare a sustained-release pharmaceutical composition. However, the sustained release profile of formulations described in U.S. Pat. No. 5,721,359 is not readily predictable and reproducible with respect to the release of active drug in the immediate post-production product that uses natural vegetable oils. U.S. patent application 2002/0110561 discloses sustained release formulations comprised of a) a modified liquid carrier and b) an essentially un-oxidizable carrier, wherein the ratio by volume of the modified liquid carrier to the essentially un-oxidizable carrier is between 0.01:99.99 to 90:10 that provide the composition with predictable sustained-release properties.
Despite the above teachings, there still exists a need in the art for pharmaceutical compositions that provide sustained-release delivery of a bioactive substance and wherein the release performance is predictable and reproducible immediately after manufacture of the product.